DESCRIPTION: This application requests support for a Keystone Symposia meeting entitled Regulation of Lymphocyte Signaling, organized by Arthur Weiss and Bernard Malissen, which will be held in Keystone, Colorado from March 11-16, 2012. Key individual components of signaling pathways that control lymphocyte activation have been identified. However, their specific regulation, integration within pathways, and regulation are still the subject of intense investigation; currently, they are being probed through biochemical, chemical-genetic, modeling, and imaging methods. Major hurdles still reflect our very simplistic understanding of both the kinetic parameters of the molecules involved as well as the complexity of the regulatory circuits of these signaling pathways. Moreover, it is still quite difficult to translate such information into downstream biologically important information. Consequently, the fact that therapeutics targeting these signaling pathways are still lagging is not surprising. The Keystone Symposia meeting on Regulation of Lymphocyte Signaling will highlight different methodologies and approaches aimed at developing a better integration of complex information about signaling. This information will lead towards better understanding of how the normal immune system functions and where interventions in signaling pathways can be used in diseases of the immune system. PUBLIC HEALTH RELEVANCE: Normal immune response depends on the proper transmission - or signaling - of extracellular cues to the cell. Defects in, or inappropriate regulation of, signaling pathways can result in pathologic responses or disease. The Keystone Symposia meeting on Regulation of Lymphocyte Signaling will bring together bioengineers, biochemists, biophysicists, cellular biologists, developmental biologists and translational scientists to share ideas, methodologies, and to identify major problems in the field of signaling in the immune system. The meeting will span the most fundamental insights that come from detailed molecular understandings of how molecules of the immune system function to applications of signaling insights in systems biology to therapeutics.